Kasi V. Somayajula

Intramolecular hydrogen transfer reactions of o-(bromophenyl)dialkylsilyl ethers. Preparation of rapamycin-d1

Abstract Radical translocations of o-(bromophenyl)dimethylsilyl ethers are efficient, but yields of α-silyloxy alkyl radicals formed by 1,5-hydrogen transfer are limited to 65-90% by competing 1,6- and 1,7-hydrogen transfers. Similarities in substituents effects on 1,5-hydrogen transfers and radical cyclizations are identified.

Electrospray mass spectrometry of trans-[Ru(NO)Cl(dpaH)2]2+ (dpaH=2,2′-dipyridylamine) and ‘caged NO’, [RuCl3(NO)(H2O)2]: loss of HCl and NO from positive ions versus NO and Cl from negative ions

The positive ion electrospray mass spectrometry (ESI-MS) of trans-[Ru(NO)Cl)(dpaH)2]Cl2 (dpaH=2,2′-dipyridylamine), obtained from the carrier solvent of H2O–CH3OH (50:50), revealed 1+ ions of the formulas [RuII(NO+)Cl(dpaH)(dpa)]+ (m/z=508), [RuIIICl(dpaH)(dpa−)]+ (m/z=478), [RuII(NO+)(dpa)2]+ (m/z=472), [RuIII(dpa)2]+ (m/z=442), originating from proton dissociation from the parent [RuII(NO+)Cl(dpaH)2]2+ ion with subsequent loss of NO (17.4% of dissociative events) or loss of HCl (82.6% of dissociative events). Further loss of NO from the m/z=472 fragment yields the m/z=442 fragment. Thus, ionization of the NH moiety of dpaH is a significant factor in controlling the net ionic charge in the gas phase, and allowing preferential dissociation of HCl in the fragmentation processes. With NaCl added, an ion pair, {Na[RuII(NO)Cl(dpa)2]}+ (m/z=530; 532), is detectable. All these positive mass peaks that contain Ru carry a signature ‘handprint’ of adjacent m/z peaks due to the isotopic distribution of 104Ru, 102Ru, 101Ru, 99Ru, 98Ru and 96Ru mass centered around 101Ru for each fragment, and have been matched to the theoretical isotopic distribution for each set of peaks centered on the main isotope peak. When the starting complex is allowed to undergo aquation for two weeks in H2O, loss of the axial Cl− is shown by the approximately 77% attenuation of the [RuII(NO+)Cl(dpaH)(dpa)]+ ion, being replaced by the [RuII(NO+)(H2O)(dpa)2]+ (m/z=490) as the most abundant high-mass species. Loss of H2O is observed to form [RuII(NO+)(dpa)2]+ (m/z=472). No positive ion mass spectral peaks were observed for RuCl3(NO)(H2O)2, ‘caged NO’. Negative ions were observed by proton dissociation forming [RuII(NO)Cl3(H2O)(OH)]− in the ionization chamber, detecting the parent 1− ion at m/z=274, followed by the loss of NO as the main dissociative pathway that produces [RuIIICl3(H2O)(OH)]− (m/z=244). This species undergoes reductive elimination of a chlorine atom, forming [RuIICl2(H2O)(OH)]− (m/z=208). The ease of the NO dissociation is increased for the negative ions, which should be more able to stabilize a RuIII product upon NO loss.

1H NMR and electrospray mass spectrometry of the mono-ionized bis(2,2'-bis(4,5-dimethylimidazole)chloronitrosylruthenium(II) complex ([Ru(NO)Cl(LH2)2]+, LH2 = 2,2'-bis(4,5-dimethylimidazole)

The reaction of RuCl3(NO)(H2O)2 with 2 equiv. of LH2=2,2′-bis(4,5-dimethylimidazole) in refluxing ethanol generates cis-[Ru(NO)Cl(LH2)2]2+ (1), analogous in structure to cis-[Ru(NO)Cl(bpy)2]2+, as the chloride salt. In 1, the methyl groups are differentiated into eight different 1H NMR magnetic environments. Substitution of 4,5-dimethyl-2,2′-biimidazole (L′H2), an 11.1% impurity in commercial LH2, occurred randomly with the undecorated ring diminishing the intensity of all eight resonances equally. The methyl group of the “out-of-plane” ring that hangs over the π orbitals of the NO+ ligand (CH3(6)) is shifted most upfield from 2.19 ppm of free LH2 and is assigned to the 1.23 ppm resonance. With the aid of 2-D NMR methods, we assign the following shifts. The ring donor opposite the {Ru(NO)}3+, CH3(7), should experience the greatest withdrawing influence, and is assigned as the origin of the 2.50 ppm resonance. Its ring partner, CH3(5), placed below another ring current, is assigned to the resonance at 2.13 ppm. 2-D NMR methods support the assignments of 1.39 ppm to CH3(1) and 2.09 ppm to CH3(2), the “in-plane-near” CH3 groups; 2.36 and 2.34 ppm to “in-plane-remote” CH3(3) and CH3(4); a 2.47 ppm shift is assigned to the remaining CH3(8). Because of the presence of the impurity L′H2 which has a substitution rate advantage (ca. 2.14-fold) due to a lower steric barrier for the unmethylated ring, the isolated product contained 62.4% (1a) [Ru(NO)Cl(LH2)2]Cl2, 31.9% (1b) [Ru(NO)Cl(LH2)(L′H2)]Cl2, and 5.7% (1c) [Ru(NO)Cl(L′H2)2]Cl2. The ESI MS spectrum exhibits parent 1+ ions (2a–c) in which one of the imidazole rings has been deprotonated. Thus, eight-line patterns for RuCl-containing fragments appear for m/z with z=1+ centered about 546 (2a), 518 (2b) and 490 (2c) in the intensity ratios of 1.000:0.511:0.091, respectively. The atomic composition for 2a was shown to be RuC20H27N9OCl (m/z=540.109049) by checking the “540” line of the isotopic bundle around m/z=546. The atomic composition of 2b was established from the “512” mass as RuC18H23N9OCl (m/z=512.077748) from the isotopic bundle around m/z=518. 2a–c undergo the loss of LH2 or L′H2 with low efficiency, but few other fragmentations were observed. Notably, the loss of NO or HCl are absent. 2a–c have good π-donating imidazole and imidazolato functionalities which suppress NO loss. IR laser loss experiments on 2a in the mass spectral cavity were unable to identify a frequency value that selectively dissociates NO. Rather, complete fragmentation of the complexes 2a–c occurred at energies sufficient to induce any ligand dissociation; the parent ions being very robust. The 1H NMR data are supported by an MMFF94 energy-minimized structure for 1 and its theoretical trans isomer.

Interactions of perfluorocarbon liquids and silicone oil as characterized by mass spectrometry

BackgroundPerfluorocarbon liquids (PFCL) are used extensively in complex vitreoretinal surgery, sometimes before the placement of silicone oil (SiO). We suspected that PFCL and SiO interact physically when in opposition, potentially making their removal more difficult. The nature of some of these interactions was explored using a mass spectrometric approach in in-vitro and in-vivo samples.MethodsWe incubated silicone oil (1,000 or 5,000 centistokes viscosity) and PFCL [perfluoro-n-octane (PFO) or perfluorotributylamine] together in vitro for 6 months and performed electron impact ionization mass spectrometry (EIMS) on the PFCL to characterize interactions between the liquid phases. Packaged samples of PFCL served as controls. We also examined in vivo samples of PFO which had been retained in human eyes for several months prior to surgical removal.ResultsPerfluorocarbon liquids packaged for surgical use all contain SiO in trace amounts, possibly as a manifestation of the processes used in their manufacture. Furthermore, all PFCLs incubated with SiO showed much more prominent contamination with SiO molecular fragments. PFCL was found in the SiO phase of eyes in which both liquids were present for extended periods of time. The EIMS analysis of in vivo samples suggested that proteins coat PFCL droplets, forming micelle-like structures.ConclusionMedical-grade PFCLs contain small amounts of SiO, and PFCLs dissolve small amounts of oil into solution over time. Interactions between retained vitreous substitutes may have clinical relevance.

Use of a nitrocellulose matrix in laser mass spectrometry

SummaryA simple method for obtaining laser mass spectra (LMS) of liquids is described using a nitrocellulose membrane or fibrous material as the sample substrate. Laser mass spectra of liquids are presented along with those of solutes in aqueous systems. The use of a liquid matrix with the laser soft ionization method enhances molecular ion formation. Results are presented for charge-transfer derivatization and the influence of solution pH on LMS.

Determination of Water Loss Mechanism in Amine Terminous Amino Acids Using Laser Mass Spectrometry

The water loss process in Laser Mass Spectrometry of amine terminal amino acids was studied. Water loss is proposed to occur via a thermal decomposition mechanism for a protonated amino acid forming a protonated lactam ring. The magnitude of the water loss peak is correlated with the stability of the protonated lactam ring. Semi-empirical MNDO calculations of the heat of reaction of a protonated amino acid forming a protonated lactam ring and water support the correlation. The substrate (matrix) appears to have little effect on the process; results are essentially the same with the use of different substrates and sample preparation methods.

Tris (perfluoroalkylethyl)silyl alkyl amines as calibration standards for electron ionization mass spectrometry in the mass range of 100-3000 Da

A new fluorinated compound mixture has been developed for the calibration of the double focusing mass spectrometer in the mass range of 100–3000 Da in the positive electron ionization (EI) mode. Current calibration standards for EI have either limited mass range [perfluorotributylamine (PFTBA), perfluorokerosene (PFK), s-triazines (TRIS)] or poor peak intensities with significant chemical background in the instrument for several days (perfluoroalkyl phosphazine). The newly synthesized fluorinated silyl alkyl amines mixture is proposed as a reference/calibration standard for EI-MS. This standard produced abundant parent and fragment ions across the entire mass range without any memory effect.